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Simplified, affordable tools to diagnose active hepatitis C virus (HCV) infection are needed to scale up treatment. This study evaluated the analytical performance of HCV core antigen (HCVcAg) detection in samples of plasma and dried venous blood spots (DBSs). Paired plasma and DBS samples were prepared from remnant diagnostic samples, and plasma HCV RNA and HCVcAg were quantified. Sensitivity and specificity for HCVcAg (>3 fmol/L) at two HCV RNA thresholds (≥15 and ≥3000 IU/mL) were calculated. Of 120 paired samples tested, 25 had nonquantifiable HCV RNA and 95 had quantifiable HCV RNA. The median HCV RNA level in plasma was 5.6 log₁₀ IU/mL (interquartile range: 5.2 to 6.2). The median HCVcAg levels in plasma and DBS samples were 2.3 log₁₀ fmol/L (interquartile range: 0.1 to 3.1) and 1.1 log₁₀ fmol/L (interquartile range: 0.0 to 1.9), respectively. For diagnosing HCV RNA …